2NYJ

Crystal structure of the ankyrin repeat domain of TRPV1

2NYJ の概要

• エントリーDOI: 10.2210/pdb2nyj/pdb
• 分子名称: Transient receptor potential cation channel subfamily V member 1, ADENOSINE-5'-TRIPHOSPHATE (2 entities in total)
• 機能のキーワード: trpv1, ankyrin repeat domain, transport protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cell junction, synapse, postsynaptic cell membrane ; Multi-pass membrane protein : O35433
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30946.43

構造登録者

Jin, X.,Gaudet, R. (登録日: 2006-11-20, 公開日: 2007-07-03, 最終更新日: 2023-12-27)

主引用文献

Lishko, P.V.,Procko, E.,Jin, X.,Phelps, C.B.,Gaudet, R.
The Ankyrin Repeats of TRPV1 Bind Multiple Ligands and Modulate Channel Sensitivity.
Neuron, 54:905-918, 2007

PubMed Abstract: TRPV1 plays a key role in nociception, as it is activated by heat, low pH, and ligands such as capsaicin, leading to a burning pain sensation. We describe the structure of the cytosolic ankyrin repeat domain (ARD) of TRPV1 and identify a multiligand-binding site important in regulating channel sensitivity within the TRPV1-ARD. The structure reveals a binding site that accommodates triphosphate nucleotides such as ATP, and biochemical studies demonstrate that calmodulin binds the same site. Electrophysiology experiments show that either ATP or PIP2 prevent desensitization to repeated applications of capsaicin, i.e., tachyphylaxis, while calmodulin plays an opposing role and is necessary for tachyphylaxis. Mutations in the TRPV1-ARD binding site eliminate tachyphylaxis. We present a model for the calcium-dependent regulation of TRPV1 via competitive interactions of ATP and calmodulin at the TRPV1-ARD-binding site and discuss its relationship to the C-terminal region previously implicated in interactions with PIP2 and calmodulin.

PubMed: 17582331
DOI: 10.1016/j.neuron.2007.05.027

実験手法

X-RAY DIFFRACTION (3.2 Å)